The Cell Response and Regulation (CRR) Program is a laboratory-based, basic science program focused on deciphering cellular mechanisms that underlie cancer development and progression. Our discovery science supports HCI's unified goal of individualized oncology by providing new insights into cancer pathways and potential biomarkers. Through transdisciplinary collaborative research, CRR members contribute to further advances in cancer prevention, prognostics, diagnostics, and therapy. Research interests focus on: 1) mechanisms and regulation of cell turnover, including apoptosis in epithelium, apoptotic dysregulation in cancer, mitotic execution, and cancer stem cells; and 2) tumor microenvironment, including cell migration, adhesion, metastasis, angiogenesis, oxidative stress, and cell-matrix interactions. The CRR members employ a variety of strategies to characterize normal cell behavior and to study genes, mechanisms, and pathways involved in cancer. Members capitalize on several animal models, such as planaria, fruit flies, zebrafish, and mice, to characterize stem cell, somatic cell, and tumor cell behavior in an organismal context. Major achievements include identification of molecular pathways and tumor suppressors important in stem cells, translation of discoveries in metastasis to prognostics for breast cancer, and pre-clinical validation of a novel chemopreventive strategy for melanoma. By creating ties to disease focus groups and recruiting physician-scientists, the CRR helps move basic research findings toward clinical translation. Co-led by Douglas Grossman, MD, PhD, and Katharine Ullman, PhD, the Program has 25 members from 13 departments and three colleges. Active recruitment efforts have led to 10 new members in the last two years. Notably, almost a quarter of CRR members are physician-scientists, bringing added clinical perspective. As of December 2008, CRR members had $6.5M in peer-reviewed annual direct costs for research projects, including 13% from NCI. Since July 2003, their research has been reported in 202 publications of which 11% were intra- and 31 % were inter-programmatic collaborations. Over 95% of members have peer-reviewed funding; distinguished awards include a new HHMI investigator, a DOD Era of Hope Scholar, and an NIH New Innovator. The Cancer Center enhances the Program's goals by providing state-of-the-art facilities, shared resources, programmatic funds, and support for recruitments. In turn, the CRR adds value to HCI through guiding shared resource development and faculty recruitment, and training and mentoring future cancer researchers. Over the next five years, the CRR Program will continue to foster synergistic cancer-focused research and will build on current strengths, particularly in stem cells and in cell migration/metastasis. We will also continue to promote the high priority of bridging basic discoveries to clinical applications.